indicates collagen within the degraded bone matrix. The plasmalemma of
the osteoclast adjacent to the resorbing bone surface is thrown into folds
and villous-like processes with tips that reach and even enter the bone surface
(ruffled border). The osteoclast is attached to the bone surface, and the resorp-
tion area is sealed off by the presence of contractile proteins in the cytoplasm
lateral to the site of the ruffled border. The basolateral membrane of the osteo-
clast posseses a Na+,K+-ATPase pump as do all human cells.
Osteoclasts are of hematopoietic origin and arise from the monocytic lin-
eage. Osteoclasts are responsive to a number of hormones including parathy-
roid hormone (PTH), calcitonin, and 1, 25(OH) 2-vitamin D3. PTH is the
major regulator of osteoclastic activity, increasing the number of osteoclasts as
well as ruffled-border activity. The osteoclasts respond to low serum Ca^2 +by
removing calcium from bone. PTH receptors are located on osteoblasts, not
osteoclasts(answer d),and so PTH affects osteoblasts to release soluble fac-
tors (RANK-L and M-CSF) that stimulate osteoclasts. Vitamin D receptors are
also present on osteoblasts and absent from the plasma membrane of osteo-
clasts(answer c).This indirect receptor effect links the osteoblast and osteo-
clast in the so-called “ARF cycle” [Activation of osteoclasts → Resorption→
Formation of new bone]. Calcitonin is only responsible for transient changes
in bone resorption. In the presence of high Ca^2 +, calcitonin is synthesized and
released from C (interfollicular, parafollicular) cells of the thyroid, which
decreases ruffled-border activity. Calcitonin receptors are located on osteo-
clasts. Long-term responses to elevated Ca^2 +are mediated by lowering of PTH
levels rather than increased calcitonin production. This is exemplified in
patients with an absence of calcitonin secretion (e.g., after thyroidectomy), or
with stimulated levels of calcitonin (e.g., in medullary thyroid carcinoma)
who exhibit relatively normal bone metabolism. However, calcitonin mea-
surements are an important tool in the diagnosis of medullary thyroid carci-
noma, a malignancy of thyroid cells. Calcitonin is also used as a nasal spray for
osteoporosis when patients cannot tolerate bisphosphonates. Bisphospho-
nates are analogues of pyrophosphate and the primary means of treating
osteoporosis and Paget’s disease. They function by inhibiting osteoclastic
activity through apoptosis of osteoclasts.
109.The answer is e.(Kumar, pp 1304–1309.)Arthritis involves inflamma-
tory changes in a joint. LDC suffers from rheumatoid arthritis; an autoim-
mune disease in which a rheumatoid factor (RF) composed of heterologous
autoantibodies directed against serum gamma globulin (IgG) appears.
208 Anatomy, Histology, and Cell Biology